- The Food and Drug Administration was supposed to decide by early March whether to approve a closely watched and controversial treatment for Alzheimer's disease. But on Friday, the treatment's developer, Biogen, said that decision could take up to three months longer because of additional information submitted at the agency's request.
- While regulatory delays can be a cause for concern, investors took a largely positive view of Friday's update. In November, a team of independent advisors to the FDA sharply criticized the data supporting Biogen's drug, known as aducanumab, which left investors fearful of an outright rejection. That the agency has now moved the approval deadline back to June 7 suggests to some that it wants to authorize aducanumab. Biogen's share price was up about 8% midday Friday.
- If approved, aducanumab would be the first marketed drug meant to alter the course of Alzheimer's, a title Wall Street analysts believe will translate to billions of dollars in annual sales. However, mixed and, by some accounts, confusing clinical data have raised questions about whether the drug actually offers a positive effect on patients' daily lives.
Aducanumab has taken one of the most winding paths of any drug in recent history.
After going through initial clinical testing, Biogen pushed two doses of the drug into a pair of large, identically-designed studies meant to prove its merit in early Alzheimer's patients. The studies, named ENGAGE and EMERGE, started a month apart in the late summer of 2015. Biogen amended the studies a few times over the following few years, but the first major, course-changing event for aducanumab didn't come until March 2019.
Then, Biogen revealed that a pre-planned, interim look at the data suggested aducanumab was unlikely to succeed in either study. The company decided to discontinue them both as a result.
Just seven months later, however, Biogen reversed course. Executives said that further analysis with more data showed the higher dose of aducanumab had hit the main goal of the EMERGE trial by slowing patients' cognitive decline. Though ENGAGE still didn't succeed, Biogen claimed there were enough positive findings from the trials to ask the FDA for approval. The company submitted its approval application in July 2020, and was told to expect a decision by March 7, 2021.
In the months since that submission, it's become clear that much of Biogen's confidence in aducanumab stems from the FDA, which worked closely with the company as it reassessed results from the two studies.
In fact, the FDA's clinical reviewers have been uncharacteristically bullish about the data, standing largely in opposition with agency statisticians who were critical of the ways Biogen collected and examined it. That led to a brief period when investors thought approval was more than likely.
However, when the FDA sought advice from a committee of Alzheimer's experts in November, the panelists strongly opposed aducanumab's approval and called out the agency for its apparent eagerness to accept mixed results. While the FDA isn't required to follow advisers' recommendations, it typically does.
This push and pull has left aducanumab's approval chances in limbo. As analysts at Stifel point out, "the whole aducanumab regulatory saga has been a challenging guessing game from the beginning."
Pushing back the drug's approval deadline will keep that game going longer.
Some see the delay as a good sign for aducanumab. Evercore ISI analyst Umer Raffat noted how, when the FDA has overturned "overwhelmingly negative" opinions from advisers in the past, it's done so because it received new, meaningful data. In Biogen's case, this new data could be from EMBARK, a long-term extension study of aducanumab.
Raffat recently told BioPharma Dive that, should the FDA extend its review time, his estimate for the probability of aducanumab's approval would go from below 50% up to 70%. "Why? Because if the [deadline's] extended, that's the most direct hint that Biogen just submitted data from EMBARK. And that would mean maybe FDA is looking at more data beyond what the [advisers] had."
Others aren't so sure. Recent criticisms of the FDA, along with a dire need for public trust amid the fast development and clearance of coronavirus vaccines, has put an immense amount of pressure on the agency to make decisions based on science.
"We think submission of EMBARK data is triggering the extension, but that ultimately it is more likely cover to let a thorough internal process play out at FDA," wrote Brian Skorney, an analyst at Baird who's been bearish on aducanumab.
"Given the new review timeline, [President Joseph] Biden's FDA commissioner will now fully own this review decision," Skorney added, referring to the fact that the administration has yet to decide whether acting commissioner Janet Woodcock, or someone else, will file the role full time.
"Scientifically, rejection is the only answer and we continue to believe the policitical winds also, once again, favor an evidence-based approach."